Breaking bad blood: how rogue neutrophils help lung cancer spread

Lung cancer remains a leading global health concern, responsible for the highest number of cancer-related deaths worldwide. Central to its development is the tumor microenvironment, which involves a complex interplay with immune cells such as neutrophils. Initially perceived as beneficial due to their anti-tumor activities in early cancer stages, neutrophils are now understood to play a dual role, potentially enhancing cancer metastasis under the influence of the tumor surroundings.

A pioneering study (DOI: 10.20892/j.issn.2095-3941.2023.0248) from Xuzhou Medical University, detailed in the February 2024 issue of Cancer Biology & Medicine, unveils a novel mechanism by which neutrophils accelerate lung cancer progression. This research underscores the pivotal function of neutrophils—typically the first responders to inflammation—as they assume pro-tumoral roles within the cancer microenvironment, thereby significantly influencing the dynamics of cancer metastasis.

The investigation explores the roles of PARP-1/Alox5/MMP9 axis in regulating lung cancer-associated neutrophil activation and thus promoting lung cancer progression. Activated by lung cancer cells, neutrophils engage PARP-1, which subsequently collaborates with another protein, ALOX5. This interaction is crucial as it boosts the production of MMP-9, an enzyme vital for degrading tissue structures and promoting cancer invasion and metastasis. Through techniques such as immunohistochemistry, the study examines neutrophil infiltration in lung cancer tissues and employs in vitro assays to analyze their impact on lung cancer cell behaviors. Gene knockdown and pharmacological inhibition of PARP-1 further elucidate its role in this process. Supported by validation in mouse models, the results indicate that blocking PARP-1 could markedly reduce tumor growth, illuminating the complex relationship between the immune system and cancer while pinpointing synergistic inhibition of PARP-1 could be benefit for lung cancer treatment.

Dr. Junnian Zheng, the lead author of the study, comments, “This research not only enhances our comprehension of the biological interactions between lung cancer cells and neutrophils but also paves the way for new targeted therapies that could interrupt these interactions and potentially elevate patients’ outcomes.”

These findings have significant implications, suggesting that targeting the PARP-1-ALOX5-MMP-9 pathway might be a promising approach to suppress the tumor-favoring activities of neutrophils in lung cancer. This strategy could lead to innovative therapies that slow lung cancer progression and bolster the effectiveness of current treatments.





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Funding information

This work was supported by grants from the National Key R&D Program of China (Grant No. 2018YFA0900900), the National Natural Science Foundation of China (Grant Nos. 82273334, 82203172, 81871869, and 81400055), the Jiangsu Province Social Development Key Projects (Grant Nos. BE2020641 and BE2020640), the Xuzhou Medical University Excellent Talent Research Start-up Fund (Grant No. RC20552157), and the Jiangsu Province Capability Improvement Project through Science, Technology and Education (Grant No. CXZX202234). The project was funded by the China Postdoctoral Science Foundation (Grant No. 2023M732970).

About Cancer Biology & Medicine

Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 5.5, 5 year IF 6.1), with all full texts freely visible to clinicians and researchers all over the world (

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